#3704 EU REGION-SPECIFIC CARDIOVASCULAR EVENT DATA FOR DAPRODUSTAT IN ASCEND-D AND ASCEND-ND

Abstract

Abstract Background and Aims Daprodustat (GSK1278863) is a hypoxia-inducible factor prolyl hydroxylase inhibitor under investigation for the treatment of anaemia of chronic kidney disease. Phase 3 studies in dialysis (ASCEND-D) and non-dialysis (ASCEND-ND) patients demonstrated the non-inferiority of daprodustat vs recombinant human erythropoietin (rhEPO) control (in ASCEND-D) or darbepoetin alfa (ASCEND-ND) control in terms of the mean change in haemoglobin levels between Weeks 28 and 52 versus baseline and the first occurrence of a composite major adverse cardiovascular (CV) event (MACE) [1, 2]. Post-hoc analyses were conducted to evaluate prespecified CV endpoints for patients enrolled in these studies from participating countries in Europe (EU patients) versus elsewhere (non-EU patients). Method Post-hoc time to the first adjudicated MACE (death from any cause, non-fatal myocardial infarction or non-fatal stroke), time to the first adjudicated MACE or thromboembolic event (TEE; deep vein thrombosis, pulmonary embolism or vascular access thrombosis), and time to the first adjudicated MACE or hospitalisation for heart failure (HHF) were analysed for EU (enrolled from Austria, Belgium, Bulgaria, Czech Republic, Denmark, Estonia, France, Germany, Greece, Hungary, Italy, the Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden and the UK; not all countries participated in both studies) and non-EU (all other participating countries) patients. Hazard ratios (HRs) and associated 95% confidence intervals were calculated to evaluate the likelihood of CV events with daprodustat versus alternative therapy in both studies. HRs for EU and non-EU patients were compared for each endpoint in each study and p-values were calculated to assess the statistical significance of observed differences. Significance was defined at the 10% level (interaction p-value <0.1). Results ASCEND-D included 415 EU patients and 1072 non-EU patients randomised to daprodustat, and 440 EU and 1037 non-EU patients randomised to rhEPO. ASCEND-ND included 410 EU patients and 1527 non-EU patients randomised to daprodustat, and 407 EU and 1528 non-EU patients randomised to darbepoetin alfa. No significant heterogeneity was observed between EU and non-EU patients in terms of the prespecified CV endpoints (p≥0.1979). In ASCEND-D and ASCEND-ND, the results for MACE, MACE+TEE and MACE+HHF for the EU subgroup were consistent with the non-EU subgroup (Table), as well as with the co-primary analysis [1, 2]. Efficacy and additional safety data for EU versus non-EU patients are being explored and will be included in the subsequent presentation. Conclusion Non-inferiority in terms of the first occurrence of MACE was demonstrated for daprodustat versus rhEPO in ASCEND-D and versus darbepoetin alfa in ASCEND-ND.1,2 Results for EU and non-EU patients in the current analysis were consistent with the global outcomes from both studies.